Viral hepatitis

1. Viral hepatitis
 pathology : inflammation ( degeneration or necrosis) of the liver parenchyma by viruses
 clinical : jaundice , fever , malaise , tender hepatomegaly
 LAB : abnormal liver function test
Classifications:
 Hepatotoxic viruses : ( hepatitis is a primary disease ) HAV, HBV, HCV, HDV ,HEV,HGV
 Non Hepatotropic viruses: ( hepatitis is apart of C/P) CMV , EBV , HIV
NB : HBV is the only Double strand DNA virus , the others (A, C,D,E) are single strand RNA
Hepatitis A virus (HAV)
Etiology & epidemiology
 Causative organism: HAV, enterovirus , non-enveloped single-stranded RNA virus , one
serotype
 Route of spread: feco-oral. via food& water . ( virus excreted only in stools , not body
fluids)
 Source of infection: cases only (no carriers).
 Mode of transmission: by contaminated food & water
 Infectivity period: from late incubation period & within 2 wks of disease onset.
 Infection in late pregnancy doesn’t affect the newborn infant (no perinatal transmission )
Pathogenesis :
 Liver cell damage or necrosis. (release of hepatic enzymes)
 Bile canaliculi disruption (regurgitation of conjugated bilirubin to blood  ↑ direct bilirubin in blood)
 Diminished conjugation process ( ↑ indirect bilirubin in blood)
 Diminished production of coagulation factors ( prolonged PT )
Pathology:
 Centrilobular degeneration & necrosis
 Parenchyma & portal tracts infiltration by inflammatory cells
Clinical features :
 IP: 4 wks ( range 2-6wks)
 commonest age : school age 6-12 yrs
 Most children have asymptomatic infection. 30-80%
 Symptomatic infection ( icteric hepatitis ) has 3 phases:
1-Pre-icteric phase:
 fever , anorexia , nausea , vomiting & abdominal pain
2-Icteric phase: -
 Jaundice, dark urine, pale stool.
 Enlarged tender liver, splenomegaly in 20%.
 improvement of constitutional manifestations ( fever , nausea , abd pain ,,,,,,,,)

2. 2- convalescence phase:
 Gradual improvement ( jaundice & hepatomegaly)
laboratory diagnosis :
 ↑ Total serum bilirubin.( mainly direct) ( usually total < 10 mg/dl)
 Positive bilirubin ( cholebilirubin) in urine ( normally absent)
 ↑serum transaminase ALT, AST by several times. (in thousands , these↑↑ not correlate with prognosis)
 PT (to assess the extent of liver injury) , prolongation is a serious sign mandating hospitalization
 hepatitis markers :
 Anti-HAV IgM: appear in serum at the onset of symptoms ( acute infection) & disappear after 4 mo.
 Anti-HAV IgG: appear during convalescence ( immunity ) & persists for years.
 Atypical presentation & complications :
1-Acute fulminant hepatitis (acute liver cell failure):
2-Aplastic anemia:
 Very rare transient complication but may be fatal
 Due to bone marrow depression. -death is usually due to serious infection 2ry to ↓immunity.
3- Cholestatic hepatitis
 picture of obstructive jaundice (due to hepatocyte edema & obstruction of biliary flow )
 Deep dark urine , pale stool , olive green jaundice, pruritus ( bile salts) and constitutional symptoms
 Waxes and wanes over several months ( 3-4 mo.)
 ↑ direct bilirubin & ALP
4- Relapsing hepatitis:
 Occurs in 10% , 4 months after the initial episode with full recovery
5- Anicteric hepatitis
 Similar to viral gastroenteritis
 Common in infancy
 No jaundice
 Constitutional symptoms ( anorexia , nausea , abdominal pain, vomiting , diarrhea )
Treatments of hepatitis A :
 Supportive treatment, no specific therapy
 balanced diet
 Iv fluids for severe vomiting
 Avoid antiemetic ( metoclopramide -- extrapyramidal manifestation )
Prevention:
 HAV Ig for close contacts in nurseries & institutions during outbreaks
 Hepatitis A vaccine: Havrix (Inactivated HAV vaccines) approved for > 12 mo
Dose : 0.5ml Upper arm . at 18 mo , 2 yrs
Comment:
 HAV cause mild-to-moderate illness (Severe illness means hepatitis of another cause
or an atypical course)
 It doesn't cause chronic active hepatitis or carrier state
Hepatitis B
Etiology & epidemiology
 Causative organism:
o HBV, an-enveloped double-stranded DNA virus
o Has 3 antigen (HBsAg,HBcAg,HBeAg) ( surface – core –
envelop )
 Route of spread:
o parenteral by needle & IV equipment ( blood & products)
o perinatal from mother to her newborn baby
o sexually ( semen , vaginal secretion )
 Source of infection:
o carriers ( HBsAg + ve)
o Drug abuser
o Blood & blood products
o Homosexuals
o Hemodialysis patients

3.  Mode of transmission :
o Perinatal : from mother( HBsAg +ve 40%)( both HBsAg &HBeAg+ve 90%) to her baby during delivery
o Parenteral : contaminated syringes , needles, blood& blood products , hemodialysis , dental care
o Direct : biting by infected person , accidental contamination( shaving , acupuncture , tattoo ----)
o sexual : infected semen & vaginal secretion
o breast milk has no significant risk ( virus is secreted in almost body secretion but only blood , serum , semen ,
vaginal secretion are infectious)
NB : High risk groups :
Medical personnel (surgeons, dentists, lab ) , hemophilic , thalassemic , homosexual , drug abuses , hemodialysis P
Clinical features: similar to HAV with some differences
Clinical features of acute hepatitis A & B &C
Items Hepatitis A Hepatitis B Hepatitis C
Incubation periods 2-6 wks 2-6 mo 2-6 mo
Mode of transmission Feco-oral Parenteral ( yes)
Sexual ( yes)
perinatal ( yes)
Parenteral ( yes)
Sexual ( rare )
Perinatal (uncommon 5- 15% %)
Onset Acute Gradual Gradual
Chronic infection No (Yes) 90%(newborn),
20%(children )
(Yes )25% ( the commonest cause )
Carrier No Yes Yes
Fulminant Rare Yes 1-5% Rare < 1%
Associated hepatoma No Yes Yes
Serum sickness
( rash & arthralgia)
No Yes Yes
Diagnosis Anti HAV IgM HBsAg , ANTI HBc IgM Anti HCV Ab (PCR)
Vaccines Inactivated
vaccine
Recombinant vaccine No vaccine
Treatment Supportive α interferon + lamivudine α interferon + ribavirin
Diagnosis:
Markers Nature Significance
HBsAg HB surface antigen , found on the surface of the
virus & detected in blood
Infection ( acute or chronic)
HB eAg HB e antigen , fragments of the core High infectivity (marker of viral replication)
Infection ( acute or chronic ) , disease activity
HB c Ag HB core antigen , found inside the virus Not present in circulation ( by liver biopsy )
Anti HBc Ig M
Anti HBc Ig G
IgM to core Ag
IgG to core Ag
Recent infection ( valuable single marker)
Recovered infection , chronic infection
Anti HB s Antibodies to HB sAg Recovery & immunity
Anti Hb e Antibodies to e Ag Low infectivity ( the end of viral replication)
Items Test
Acute infection Hbs Ag +ve
HB e Ag + ve
Anti HBc Ig M +ve
HBV DNA + ve (PCR )
Recovered infection ( resolved- cured) Anti HB s + ve
Anti HBc Ig G + ve
Chronic infection Hbs Ag +ve & Anti HB s - ve
Anti HBc Ig G + ve
Vaccine response Anti HB s + ve alone

4. NB :
Anti HB s + ve alone (vaccination) ( bec . vaccination contains HBsAg only , so body produce anti HBs )
Anti HB s + ve & Anti HBc Ig G + ve (resolved infection) ( virus contains core & surface )
s Ag= coincide with the onset of symptoms
e Ag =marker of replications ---- infectivity & transmission ( it is a cleavage particles of core antigen)
HbsAg ( infection ) -------------------------- after5 mo ------------------------- Anti HB s ( immunity )
During this time body tries to fight off the virus by anti Hbc Ig M then Ig G
Windows period : ( infected despite HBsAg – ve ) ( HBsAg – ve & Anti HBc IgM + ve )
Exists during the course of infection , the body tries to fight off the virus by Anti HBc IgM ,
the virus particles becomes so few that they aren’t detected by serology ( HBsAg – ve)
in fulminant B hepatitis : AntiHBc IgM is diagnostic
Anti HBc Ig G : persists for life & is the best marker for previous exposure
High rate of fulminant hepatitis occurs in combined B & D viruses

5. Antigen appears first then antibodies

6. Complications:
 Chronic hepatitis : can lead to cirrhosis & malignancy ( risk in neonates 90% - children 10% )
 Fulminant hepatitis with coagulopathy , encephalopathy & cerebral edema ( risk 1%- mortality 70%)
 membranous glomerulonephritis: rare , deposition of Hbe Ag + complement in glomerular capillaries
 Polyarteritis nodosa ( PAN )
Treatment:
 acute stage  supportive treatment
 chronic stage
 Interferon α 2 b, for recent infection & active viral replication ,it has immunomodulatory & antiviral effect,SC,for
24 wks (25-40% recovery rate )
 Oral antiviral drugs ( lamivudine) in children > 2 yrs , used for (52 wks)

7. Immunoprophylaxis:
 Immunoglobulin : ( HBIG) contains anti HBs , dose 0.5ml , given after exposure ( household , sexual contacts ,
perinatal exposure .)
 Vaccine ( HB vaccine ) - ( energix B ) : schedule vaccination
 for neonates with HbsAg + ve mother :
o HBIG + HB vaccine IM within 12 hours after birth & repeated at 1, 6 mo.
Prognosis:
 The outcome in general is favorable despite risk of fulminant hepatitis ( risk 1-5%)
 Chronic hepatitis : ( risk in neonates 90% - children 10% ) leads to liver cirrhosis & malignancy
 Chronic carrier state 5%
 Viral infection & complications are effectively controlled with vaccination
Prevention:
 Vaccination & immunoglobulins see above
 Careful handling of needles & blood
 Screening blood & its products before transfusion
https://youtu.be/sndUqE1QAKU ( HBV serology )
Hepatitis C virus ( HCV):
Clinical features of acute hepatitis A & B &C
Items Hepatitis A Hepatitis B Hepatitis C
Incubation periods 2-6 wks 2-6 mo 2-6 mo
Mode of transmission Feco-oral Parenteral ( yes)
Sexual ( yes)
perinatal ( yes)
Parenteral ( yes)
Sexual ( rare )
Perinatal (uncommon 5- 15% %)
Onset Acute Gradual Gradual
Chronic infection No Yes 90%(NB), 20%(CH) Yes 25% ( the commonest cause )
Carrier No Yes Yes yes yes yes yes yes
Fulminant Rare Yes 1-5% Rare < 1%
Associated hepatoma No Yes Yes
Serum sickness
( rash & arthralgia)
No Yes Yes
Diagnosis Anti HAV IgM HBsAg , ANTI HBc IgM Anti HCV Ab (PCR)
Vaccines Inactivated
vaccine
Recombinant vaccine No vaccine
Treatment Supportive α interferon + lamivudine α interferon + ribavirin
Etiology & epidemiology
 Causative organism:
o HCV: an-enveloped single-stranded RNA virus ,
o Has 6 genotype & several subtypes
 Route of spread:
o parenteral
 Source of infection:
o carriers
o Drug abuser
o Homosexuals
o Blood & blood products
o Hemodialysis patients
o medical personnel

8. Mode of transmission:
o Parenteral : contaminated syringes , needles, blood& blood products , hemodialysis , dental care
o Sexual : infected semen & vaginal secretion ( the 2nd
common in adult)
o Perinatal : is uncommon 5- 15%%(the 2nd
common in children )(most new cases -Perinatal )
Prevalence (groups at risk) : hemophiliacs 90% , thalassemiacs 10% , hemodialysis patients 40%
Clinical features:
 similar to other viral hepatitis
 is the most likely hepatotropic virus to cause chronic hepatitis
Diagnosis:
 serum transaminase
 markers :
 HCV antigen by PCR ( detection of RNA virus) + ve after 2wks post infection
 HCV antibodies by PCR + ve after 1- 3mo post infection ( positivity = chronic hepatitis)
Treatment:
 Interferon α 2 b, it has immunomodulatory & antiviral effect
 Oral antiviral drugs ( ribavirin )
 New antiviral drugs : sovaldi ( sofosbuvir ) olysio (simeprevir ) ‫الصحة‬ ‫وزارة‬ ‫أدوية‬
Prevention:
 no vaccine is available -screening of blood & blood products - breast feeding is allowed
‫إبراهيم‬ ‫محمد‬ ‫د‬ ‫اعداد‬